The mammalian renal system serves primary roles both in the removal of catabolic waste products from the bloodstream and in the maintenance of fluid and electrolyte balances in the body. Renal failure is, therefore, a life-threatening condition in which the build-up of catabolites to and other toxins, and/or the development of significant imbalances in electrolytes or fluids, may lead to the failure of other major organs systems and death. As a general matter, renal failure is classified as “acute” or “chronic” As detailed below, acute renal failure typically involves a rapid, drastic, life-threatening loss of renal function over a period of a few hours to several weeks. In contrast, chronic renal failure typically involves a slow, progressive loss of renal function over a period of months to years, during which time the subject's life is not immediately threatened.
Acute renal failure is characterized by an abrupt cessation or substantial reduction of renal function, and is typically diagnosed by relatively rapid increases in blood urea nitrogen (BUN) or serum creatinine levels over a period of a few hours or days. In as many as 90-95% of cases, acute renal failure may be secondary to trauma, surgery or another acute medical condition. Generally speaking, acute renal failure may be due to pre-renal, post-renal, or intrinsic renal causes. Pre-renal causes (e.g., decreased cardiac output, hypovolemia, altered vascular resistance) and post-renal causes (e.g., obstructions or constrictions of the ureters, bladder or urethra) do not involve direct damage to the kidneys but; by affecting the flow of blood to the kidneys or the flow of urine from the kidneys, may lead to significant permanent and/or progressive damage to renal tissues. On the other hand, acute renal failure may be due to intrinsic renal causes which involve a more direct insult or injury to the kidneys, and which also may entail permanent and/or progressive damage to the nephrons or other kidney structures. Intrinsic causes of acute renal failure include but are not limited to infectious diseases (e.g., various bacterial, viral or parasitic infections), inflammatory diseases (e.g., glomerulonephritis, systemic lupus erythematosus), ischemic (e.g., renal artery occlusion), toxic syndromes (e.g., heavy metal poisoning, side-effects of antimicrobial treatments or chemotherapy), and direct traumas.
In human acute renal failure patients, oliguria (urine output<400 ml/day) or anuria (urine output<50 ml/day) may be present in 50-70% of cases, BUN levels may climb 10-20 mg/dL/day or faster, plasma creatinine levels may climb 0.5-1.0 mg/dL/day, and metabolic acidosis is almost always present. If not treated, the electrolyte and fluid imbalances (e.g., hyperkalemia, acidosis, edema) associated with acute renal failure may lead to life-threatening arrhythmia, congestive heart failure, or multiple organ system failures. Due to the severity of acute renal failure, episodes rarely last longer than several weeks without mortality and are treated on an in-patient basis.
A need remains, therefore, for treatments which will prevent, inhibit, delay or alleviate the permanent or progressive loss of renal function which may result from acute renal failure.